Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Monday Speaker Abstracts

AN ANISOTROPIC CONTINUUM MODEL THAT CAPTURES MOLECULAR-LEVEL PROTEIN-MEMBRANE INTERACTIONS Timothy S. Carpenter 1 ; Tomas Oppelstrup 1 ; Liam Stanton 2 ; Helgi Ingolfsson 1 ; Tugba Ozturk 1 ; Jeremy Tempkin 1 ; 1 Lawrence Livermore National Laboratory, Livermore, CA, USA 2 San Jose State University, San Jose, CA, USA Membrane proteins have important cellular roles and comprise the vast majority of all approved drug targets. These proteins interact strongly with lipids, and protein function can be affected by local lipid compositions. Furthermore, the interactions between proteins and their surrounding membranes can be distinctly anisotropic, with different patterns of lipid enrichments on opposite sides of the protein. These anisotropic patterns can have a large impact, for instance in driving protein-protein aggregation and facilitating specific interaction interfaces. The proper exploration of these relationships requires a bilayer that is not only large enough to contain relevant compositional fluctuations but is also simulated for enough time for local lipid compositions to equilibrate around the protein. For a single protein in a complex membrane mixture, the appropriate sampling time-scales are on the order of 100s of microseconds with systems containing >5,000 lipids. This extensive computational investment is required for each subsequent variable tested – rendering wide-ranging investigation prohibitively expensive in terms of time and computing resources. To that end, we extend our work on continuum membrane models from Stanton et al. 1 to allow for nontrivial protein structure, which results in a fully anisotropic protein-lipid potential interaction. We demonstrate how our model reproduces the given lipid density fields and compare the expressive complexity gained by using anisotropic potentials for two types of complex proteins on the cell membrane. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC5207NA27344. 1 Stanton, L. G., Oppelstrup, T., Carpenter, T. S., Ingólfsson, H. I., Surh, M. P., Lightstone, F. C., & Glosli, J. N. (2023). Dynamic density functional theory of multicomponent cellular membranes. Physical Review Research, 5(1), 013080.

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